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BACKGROUND: Cow milk fat is an essential indicator for evaluating and measuring milk quality and cow performance. Growing research has identified the molecular functions of circular RNAs (circRNAs) necessary for mammary gland development and lactation in mammals. METHOD: The present study analyzed circRNA expression profiling data in mammary epithelial cells (MECs) from cows with highly variable milk fat percentage (MFP) using differential expression analysis and weighted gene co-expression network analysis (WGCNA). RESULTS: A total of 309 differentially expressed circRNAs (DE-circRNAs) were identified in the high and low MFP groups. WGCNA analysis revealed that the pink module was significantly associated with MFP (r = - 0.85, P = 0.007). Parental genes of circRNAs in this module were enriched mainly in lipid metabolism-related signaling pathways, such as focal adhesion, ECM-receptor interaction, adherens junction and AMPK. Finally, six DE-circRNAs were screened from the pink module: circ_0010571, circ_0007797, circ_0002746, circ_0003052, circ_0004319, and circ_0012840. Among them, circ_0002746, circ_0003052, circ_0004319, and circ_0012840 had circular structures and were highly expressed in mammary tissues. Subcellular localization revealed that these four DE-circRNAs may play a regulatory role in the mammary glands of dairy cows, mainly as competitive endogenous RNAs (ceRNAs). Seven hub target genes (GNB1, GNG2, PLCB1, PLCG1, ATP6V0C, NDUFS4, and PIGH) were obtained by constructing the regulatory network of their ceRNAs and then analyzed by CytoHubba and MCODE plugins in Cytoscape. Functional enrichment analysis revealed that these genes are crucial and most probable ceRNA regulators in milk fat metabolism. CONCLUSIONS: Our study identified several vital circRNAs and ceRNAs affecting milk fat synthesis, providing new research ideas and a theoretical basis for cow lactation, milk quality, and breed improvement.
Subject(s)
MicroRNAs , RNA, Circular , Female , Cattle , Animals , RNA, Circular/genetics , RNA, Circular/metabolism , Milk/metabolism , RNA, Competitive Endogenous , Lactation/genetics , Lipid Metabolism/genetics , Gene Regulatory Networks , MicroRNAs/genetics , Mammals/geneticsABSTRACT
Hyperactivation of the cyclic-GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signalling pathway has been shown to be associated with the development of a variety of inflammatory diseases, and the discovery of an inhibitor of the cGAS-STING signalling pathway holds great promise in the therapeutic interventions. Epimedium flavonoid (EF), a major active ingredient isolated from the medicinal plant Epimedium, has been reported to have good anti-inflammatory activity, but its exact mechanism of action remains unclear. In the present study, we found that EF in mouse bone marrow-derived macrophages (BMDMs), THP-1 (Tohoku Hospital Pediatrics-1) as well as in human peripheral blood mononuclear cells (hPBMC) inhibited the activation of the cGAS-STING signalling pathway, which subsequently led to a decrease in the expression of type I interferon (IFN-ß, CXCL10 and ISG15) and pro-inflammatory cytokines (IL-6 and TNF-α). Mechanistically, EF does not affect STING oligomerization, but inhibits the formation of functional STING signalosome by attenuating the interaction of interferon regulatory factor 3 (IRF3) with STING and TANK-binding kinase 1 (TBK1). Importantly, in vivo experiments, EF has shown promising therapeutic effects on inflammatory diseases mediated by the cGAS-STING pathway, which include the agonist model induced by DMXAA stimulation, the autoimmune inflammatory disease model induced by three prime repair exonuclease 1 (Trex1) deficiency, and the non-alcoholic steatohepatitis (NASH) model induced by a pathogenic amino acid and choline deficiency diet (MCD). To summarize, our study suggests that EF is a potent potential inhibitor component of the cGAS-STING signalling pathway for the treatment of inflammatory diseases mediated by the cGAS-STING signalling pathway.
Subject(s)
Epimedium , Flavonoids , Membrane Proteins , Nucleotidyltransferases , Signal Transduction , Nucleotidyltransferases/metabolism , Membrane Proteins/metabolism , Animals , Signal Transduction/drug effects , Humans , Mice , Flavonoids/pharmacology , Epimedium/chemistry , Interferon Regulatory Factor-3/metabolism , Macrophages/metabolism , Macrophages/immunology , Macrophages/drug effects , Mice, Inbred C57BL , Cytokines/metabolism , THP-1 Cells , Protein Serine-Threonine Kinases/metabolism , Anti-Inflammatory Agents/pharmacology , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/drug effectsABSTRACT
PURPOSE: The purpose of this study was to investigate immunological variations between a group that received the hepatitis B vaccine and a non-vaccine group. We focused on a cohort that achieved HBsAg seroclearance after Peg-IFNα treatment of CHB. METHODS: We enrolled twenty-eight individuals who achieved HBsAg seroclearance after Peg-IFNα treatment. They were divided into two groups: a vaccine group (n = 14) and a non-vaccine group (n = 14). We assessed lymphocyte subpopulations, B cell- and T cell-surface costimulatory/inhibitory factors, cytokines and immunoglobulin levels were detected at different time points to explore immune-function differences between both groups. RESULTS: The seroconversion rate in the vaccine group at 24 weeks post-vaccination was 100%, which was significantly higher (p = 0.006) than that of the non-vaccine group (50%). Additionally, more individuals in the vaccine group exhibited anti-HBs levels exceeding 100 IUs/L and 300 IUs/L compared to the non-vaccine group (p < 0.05). The vaccine group demonstrated significantly increase total B cells and class-switched B cells at 24 weeks and plasma cells, CD80+B cells, Tfh cells, and ICOS+Tfh cell at 12 weeks, compared with baseline levels (p < 0.05). Conversely, Bregs (CD24+CD27+ and CD24+CD38high) decreased significantly at 24 weeks (p < 0.05). None of the above changes were statistically significance in the non-vaccine group (p > 0.05). Total IgG increased significantly in the vaccine group, and IL-2, IL-5, and IL-6 concentrations increased significantly at week 24 (p < 0.05). Differences in various types of cytokines and immunoglobulins in the plasma of the non-vaccine group were not significant (p > 0.05). Anti-HBs titers positively correlated with Th1/Th2 cells at 24 weeks (r = 0.448 and 0.458, respectively, p = 0.022 and 0.019, respectively), and negatively with CD24+CD38highBreg cells (r = -0.402, p = 0.042). CONCLUSIONS: After achieving HBsAg seroclearance through Peg-IFNα treatment for CHB, administering the hepatitis B vaccine significantly increased anti-HBs-seroconversion rates and antibody levels. We also observed significant immunological differences between the vaccine and non-vaccine groups. Specifically, the vaccine group exhibited significant increases in B cells, plasma cells, and Tfh cells, while Breg levels was significantly lower. These immunological changes are likely conducive to the production of anti-HBs antibodies. However, in the non-vaccine group, the observed changes were not significantlly significant.
Subject(s)
Hepatitis B Surface Antigens , Hepatitis B, Chronic , Humans , Interferon-alpha/therapeutic use , Seroconversion , Hepatitis B, Chronic/drug therapy , Hepatitis B Vaccines/therapeutic use , Cytokines , Hepatitis B Antibodies , Vaccination , Immunity , Hepatitis B e Antigens , Antiviral Agents/therapeutic use , Polyethylene Glycols/therapeutic useABSTRACT
The degradation of organic dye from waterbodies is of great significance for clean production and environmental remediation. Herein, two porphyrin-based conjugated microporous polymers (CMPs) loaded with nanoscale zerovalent iron (named as Por-CMPs-1-2@nZVI) were successfully fabricated by Sonogashira-Hagihara coupling reactions and the liquid-phase method. The as-synthesized Por-CMPs-1-2@nZVI composites were characterized by various means of analysis, and it was confirmed that Por-CMPs-1-2 loaded with nZVI had good photocatalytic performance. Calculated by ultraviolet-visible spectrum, the band-gap energies of Por-CMPs-1@nZVI and Por-CMPs-2@nZVI were 1.45 and 1.32 eV, respectively, indicating that both can be activated by visible light. The photodegradation of organic dye experiments demonstrated that Por-CMPs-2@nZVI degraded 98.0% of 10 ppm Methylene Blue (MB) within 150 min, which is higher than that of Por-CMPs-1-2 and Por-CMPs-1@nZVI. The experiment of active substance capture and mechanism of ESR confirmed that superoxide anion and hydroxyl radical were the primary valid substances in the photodegradation process of MB. In addition, the preparation of membrane materials was shown to be a successful strategy to realize engineered scale-up production.
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Developing a convenient detection method is important for diagnosing and treating obstructive sleep apnea. Considering availability and medical reliability, we established a deep-learning model that uses single-lead electrocardiogram signals for obstructive sleep apnea detection and severity assessment. The detection model consisted of signal preprocessing, feature extraction, time-frequency domain information fusion, and classification segments. A total of 375 patients who underwent polysomnography were included. The single-lead electrocardiogram signals obtained by polysomnography were used to train, validate and test the model. Moreover, the proposed model performance on a public dataset was compared with the findings of previous studies. In the test set, the accuracy of per-segment and per-recording detection were 82.55% and 85.33%, respectively. The accuracy values for mild, moderate and severe obstructive sleep apnea were 69.33%, 74.67% and 85.33%, respectively. In the public dataset, the accuracy of per-segment detection was 91.66%. A Bland-Altman plot revealed the consistency of true apnea-hypopnea index and predicted apnea-hypopnea index. We confirmed the feasibility of single-lead electrocardiogram signals and deep-learning model for obstructive sleep apnea detection and severity evaluation in both hospital and public datasets. The detection performance is high for patients with obstructive sleep apnea, especially those with severe obstructive sleep apnea.
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Sporopollenin, as the main component of the pollen exine, is a highly resistant polymer that provides structural integrity under unfavourable environmental conditions. Tetraketone α-pyrone reductase 1 (TKPR1) is essential for sporopollenin formation, catalyzing the reduction of tetraketone carbonyl to hydroxylated α-pyrone. The functional role of TKPR1 in male sterility has been reported in flowering plants such as maize, rice, and Arabidopsis. However, the molecular cloning and functional characterization of TKPR1 in cotton remain unaddressed. In this study, we identified 68 TKPR1s from four cotton species, categorized into three clades. Transcriptomics and RT-qPCR demonstrated that GhTKPR1_8 exhibited typical expression patterns in the tetrad stage of the anther. GhTKPR1_8 was localized to the endoplasmic reticulum. Moreover, ABORTED MICROSPORES (GhAMS) transcriptionally activated GhTKPR1_8 as indicated by luciferase complementation tests. GhTKPR1_8-knockdown inhibited anther dehiscence and reduced pollen viability in cotton. Additionally, overexpression of GhTKPR1_8 in the attkpr1 mutant restored its male sterile phenotype. This study offers novel insights into the investigation of TKPR1 in cotton while providing genetic resources for studying male sterility.
Subject(s)
Gene Expression Regulation, Plant , Gossypium , Plant Proteins , Pollen , Pollen/genetics , Pollen/physiology , Gossypium/genetics , Gossypium/physiology , Plant Proteins/genetics , Plant Proteins/metabolism , Flowers/genetics , Flowers/physiology , Plant Infertility/genetics , PhylogenyABSTRACT
OBJECTIVE: To investigate the factors associated with brain frailty and the effect of brain frailty in patients with anterior circulation large artery occlusion (AC-LAO). METHODS: 1100 patients with AC-LVO consecutively admitted to the Second Hospital of Hebei Medical University, North China between June 2016 and April 2018 were retrospectively analyzed. The variables associated with brain frailty and stroke outcome were analyzed by ANOVA analysis, the Mann-Whitney U test and multiple linear regression. Based on previous research. Brain frailty score comprises 1 point each for white matter hyperintensity (WMH), old infarction lesions, and cerebral atrophy among 983 participants with baseline brain magnetic resonance imaging or computed tomography. RESULTS: Among AC-LAO participants, baseline brain frailty score ≥ 1 was common (750/983, 76.3%). Duration of hypertension > 5 years (mean difference [MD] 0.236, 95% CI 0.077, 0.395, p = 0.004), multiple vessel occlusion (MD 0.339, 95% CI 0.068, 0.611, p = 0.014) and basal ganglia infarction (MD -0.308, 95% CI -0.456, -0.160, p < 0.001) were independently associated with brain frailty score. Brain frailty score was independently associated with stroke events, and higher brain frailty scores were associated with higher rates of stroke events (p < 0.001). However, brain frailty has no independent effect on short-term outcome of ACI in AC-LAO patients. CONCLUSIONS: In AC-LAO patients, older age, duration of hypertension > 5 years, and multiple vessel occlusion influenced the brain frailty score. Brain frailty score was independently associated with the occurrence of stroke events in AC-LAO patients.
Subject(s)
Brain Ischemia , Frailty , Hypertension , Stroke , Humans , Retrospective Studies , Frailty/complications , Frailty/epidemiology , Stroke/complications , Stroke/epidemiology , Brain , Arteries , InfarctionABSTRACT
The pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has had a profound impact on the global health and economy. While mass vaccination for herd immunity is effective, emerging SARS-CoV-2 variants can evade spike protein-based COVID-19 vaccines. In this study, we develop a new immunization strategy by utilizing a nanocarrier, dendritic mesoporous silica nanoparticle (DMSN), to deliver the receptor-binding domain (RBD) and conserved T-cell epitope peptides (DMSN-P-R), aiming to activate both humoral and cellular immune responses in the host. The synthesized DMSN had good uniformity and dispersion and showed a strong ability to load the RBD and peptide antigens, enhancing their uptake by antigen-presenting cells (APCs) and promoting antigen delivery to lymph nodes. The DMSN-P-R vaccine elicited potent humoral immunity, characterized by highly specific RBD antibodies. Neutralization tests demonstrated significant antibody-mediated neutralizing activity against live SARS-CoV-2. Crucially, the DMSN-P-R vaccine also induced robust T-cell responses that were specifically stimulated by the RBD and conserved T-cell epitope peptides of SARS-CoV-2. The DMSN demonstrated excellent biocompatibility and biosafety in vitro and in vivo, along with degradability. Our study introduces a promising vaccine strategy that utilizes nanocarriers to deliver a range of antigens, effectively enhancing both humoral and cellular immune responses to prevent virus transmission.
Subject(s)
COVID-19 , Nanoparticles , Humans , SARS-CoV-2 , COVID-19 Vaccines , Epitopes, T-Lymphocyte , Vaccination , Antibodies, Neutralizing , Peptides , Antibodies, ViralABSTRACT
Global population aging poses a tremendous burden on the health care system worldwide. Frailty is associated with decreased physical reserve and is considered an important indicator of adverse events in the older population. Therefore, there is growing interest in the early diagnosis and intervention of frailty, but the cellular mechanisms responsible for frailty are still not completely understood. Chronic inflammation is related to decreased physical function and increased disease risk. Additionally, multiple human and animal studies suggest that inflammation probably plays the largest role in contributing to frailty. Some inflammatory markers have been proposed to predict physical frailty. However, there are still large gaps in knowledge related to the clinical application of these markers in frail patients. Therefore, understanding the biological processes and identifying recognized and reliable markers are urgent and pivotal tasks for geriatricians. In the present review, we broadly summarize the inflammatory markers that may have potential diagnostic and therapeutic use, thereby translating them into health care for older people with frailty in the near future.
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BACKGROUND: Intrinsic capacity is the combination of individual physical and mental abilities, reflecting the aging degree of the older adults. However, the mechanisms and metabolic characteristics of the decline in intrinsic capacity are still unclear. AIMS: To identify metabolic signatures and associated pathways of decline in intrinsic capacity based on the metabolite features. METHODS: We recruited 70 participants aged 77.19 ± 8.31 years. The five domains of intrinsic capacity were assessed by Short Physical Performance Battery (for mobility), Montreal cognition assessment (for cognition), 30-Item Geriatric Depression Scale (for psychology), self-reported hearing/visual impairment (for sensory) and Nutritional risk screening (for vitality), respectively. The serum samples of participants were analyzed by liquid chromatography-mass spectrometry-based metabolomics, followed by metabolite set enrichment analysis and metabolic pathway analysis. RESULTS: There were 50 participants with a decline in intrinsic capacity in at least one of the domains. A total of 349 metabolites were identified from their serum samples. Overall, 24 differential metabolites, 5 metabolite sets and 13 pathways were associated with the decline in intrinsic capacity. DISCUSSION: Our results indicated that decline in intrinsic capacity had unique metabolomic profiles. CONCLUSION: The specific change of acyl carnitines was observed to be a feature of decline in intrinsic capacity. Dysregulation of the pentose phosphate pathway and of arginine and ornithine metabolism was strongly associated with the decline in intrinsic capacity.
Subject(s)
Arginine , Carnitine/analogs & derivatives , Pentose Phosphate Pathway , Humans , Aged , Metabolomics/methods , China , OrnithineABSTRACT
Chemotherapy is a well-established method for treating cancer, but it has limited effectiveness due to its high dosage and harmful side effects. To address this issue, researchers have explored the use of photothermal agent nanoparticles as carriers for precise drug release in vivo. In this study, three different sizes of polydopamine nanoparticles (PDA-1, PDA-2, and PDA-3) were synthesized and evaluated. PDA-2 was selected for its optimal size, encapsulation rate, and drug loading rate. The release of the drug from PDA-2@TAX was tested at different pH and NIR laser irradiation levels. The results showed that PDA-2@TAX released more readily in an acidic environment and exhibited a high photothermal conversion efficiency when exposed to an 808 nm laser. In vitro experiments on ovarian cancer cells demonstrated that PDA-2@TAX effectively inhibited cell proliferation, highlighting its potential for synergistic chemotherapy-photothermal treatment.
Subject(s)
Hyperthermia, Induced , Indoles , Nanoparticles , Ovarian Neoplasms , Polymers , Quercetin/analogs & derivatives , Humans , Female , Phototherapy/methods , Hyperthermia, Induced/methods , Ovarian Neoplasms/drug therapy , Doxorubicin/pharmacologyABSTRACT
BACKGROUND: Pneumonia has a high incidence in traumatic brain injury (TBI) patients and lacks effective treatments. Early mobilization (EM) may be a potentially effective treatment. AIM: To explore the impact of EM on TBI-related pneumonia in the neurosurgical intensive care unit (NICU). METHOD: This study was a historical control study. 100 TBI patients who received EM intervention were prospectively included as the experimental group (EM cohort), and 250 TBI patients were retrospectively included as the control group. The propensity score matching (PSM) method was employed to balance baseline and minimize potential bias. The relationship between EM and TBI-related pneumonia was investigated by univariate and multivariate logistic regression, then further determined by subgroup analysis. The influence of other variables was excluded by interaction analyses. Finally, the effect of EM on the prognosis of TBI patients was analysed by comparing the Glasgow Coma Scale (GCS) and the hospital stay. RESULTS: After screening, 86 patients were included in the EM cohort and 199 patients were included in the control cohort. There were obvious differences between the two cohorts at baseline, and these differences were eliminated after PSM, when the incidence of pneumonia was significantly lower in the EM cohort than in the control cohort (35.0% vs. 61.9%, p < .001). Multivariate logistic regression showed that EM was an independent risk factor for TBI-related pneumonia and was significantly associated with a decreased incidence of pneumonia. This correlation was present in most subgroups and was not affected by other variables (p for interaction >.05). Patients in the EM cohort had shorter length of ICU stay (6 vs. 7 days, p = .017) and higher GCS at discharge (12 vs. 11, p = .010). CONCLUSION: EM is a safe and effective treatment for TBI patients in NICU, which can reduce the incidence of pneumonia, help to improve prognosis and shorten the length of ICU stay. RELEVANCE TO CLINICAL PRACTICE: Although the utilization rate of EM is low in TBI patients for various reasons, EM is still an effective method to prevent complications. Our study confirms that a scientific and detailed EM strategy can effectively reduce the incidence of pneumonia while ensuring the safety of TBI patients, which is worthy of further research and clinical application.
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OBJECTIVE: To investigate the clinical and genetic characteristics of a case of primary ciliary dyskinesia (PCD). METHODS: We collected the clinical data on a case of PCD treated in the Department of Reproductive Medicine of Linyi People's Hospital in July 2020, detected the genes of the patient by whole-exome sequencing (WES), verified the candidate mutations by Sanger sequencing, and predicted the protein structure of the mutant gene by SWISS-MODEL. RESULTS: The proband was found with the clinical phenotypes of chronic rhinitis, bronchiectasis, visceral transposition and male infertility. WES revealed a homozygous frameshift variation of c.12890dup (p.N4297Kfs*13) in exon 74 of the DNAH5 gene, which led to the premature termination of polypeptide chain synthesis and affected the gene function. SWISS-MODEL prediction showed that some of the amino acid residues were deleted after mutation, resulting in a 3D conformational change of the protein. This variation was not recorded in the ClinVar, gnomAD and OMIM databases and, according to the relevant guidelines of the American College of Genetics and Genomics, was classified as a pathogenic variation (PVS1+PM2_P+PM3_P). CONCLUSION: The homozygous variation of the DNAH5 gene c.12890dup (p.N4297Kfs*13) may be the cause of the clinical phenotype of this case of PCD, and the above findings have enriched the variation spectrum of the DNAH5 gene.
Subject(s)
Exome Sequencing , Frameshift Mutation , Humans , Male , Axonemal Dyneins/genetics , Phenotype , Homozygote , Ciliary Motility Disorders/genetics , Exons , Infertility, Male/geneticsABSTRACT
In older adults, physical frailty and cognitive impairment contribute to adverse outcomes. However, the research on mechanisms underlying physical frailty and cognitive impairment is limited. Low-grade chronic inflammation is a characteristic of aging. Particularly, an imbalance in pro- and anti-inflammatory mechanisms may be involved in frailty and neurodegenerative disorders. Therefore, exploring the inflammatory markers of physical frailty and cognitive impairment is crucial to fully understanding these mechanisms and establishing a substantial link between these two disorders. Notably, few studies have focused on exploring inflammatory markers in both physical frailty and cognitive impairment, posing a major challenge in elucidating the link between them. Therefore, substantial efforts are required for the better prevention of physical frailty and cognitive impairment. In this review, we explored the role of inflammatory markers as a potential link between frailty and cognitive impairment.
ABSTRACT
Intrinsic capacity is the sum of an individual's physical and mental capacities, which helps determine functional ability. Intrinsic capacity decline is an important predictor of adverse health outcomes and can identify individuals at higher risk of functional decline. Aging is characterized by a decrease in physiological reserves and functional abilities. Chronic inflammation, a mechanism of aging, is associated with decreased intrinsic capacity, which may mirror the broader relationship between aging and functional ability. Therefore, it is crucial for maintaining functional ability and promoting healthy aging to study the mechanisms of intrinsic capacity decline, identify easily available markers, and make targets for intervention from the perspective of chronic inflammation. We reviewed the current research on chronic inflammation, inflammation-related markers, and intrinsic capacity. To date, there is still no inflammatory markers with high specificity and sensitivity to monitor intrinsic capacity decline. Interleukin-6, C-reactive protein, and tumor necrosis factor-alpha may potentially indicate changes in intrinsic capacity, but their results with intrinsic capacity or each intrinsic capacity domain are inconsistent. Considering the variations in individual responses to changes in inflammatory markers, it may be beneficial to explore the use of multiple analytes instead of relying on a single marker. This approach could be valuable in monitoring the decline of intrinsic capacity in the future.
Subject(s)
Aging , Inflammation , Humans , Inflammation/metabolism , Aging/metabolism , C-Reactive Protein/metabolism , Interleukin-6 , Activities of Daily LivingABSTRACT
The rapid growth of on-demand ride service platforms has made it increasingly important for these platforms to efficiently match services by understanding driver characteristics and consumer preferences. This paper aims to investigate the pricing strategy by considering the impact of consumer preference heterogeneity and the different service types offered by drivers. The findings of this study reveal the need for the platform to strike a balance between service cost and the benefits of high-quality drivers, which can be referred to as the "cost-performance ratio". If the "cost-performance ratio" that attracts high-quality drivers is high, the platform will attract high-quality drivers or drivers of all types to participate while offering differentiated services. Otherwise, the platform will only provide services through low-quality drivers. Furthermore, the platform will also consider when to offer differentiated services based on network externalities and service quality. When the network externalities of the two types of services are similar, the platform will differentiate them based on service quality differences. Overall, considering consumer preference heterogeneity, drivers of service types, and network externalities, this paper provides guidance for platforms to make optimal decisions that enhance their service offerings and improve overall customer satisfaction.
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Hepatocellular carcinoma (HCC) represents a major global health threat with diverse and complex pathogenesis. Aldo-keto reductase family 1 member B10 (AKR1B10), a tumor-associated enzyme, exhibits abnormal expression in various cancers. However, a comprehensive understanding of AKR1B10's role in HCC is lacking. This study aims to explore the expression characteristics of AKR1B10 in HCC and its correlation with clinicopathological features, survival prognosis, and tumor immune microenvironment, further investigating its role and potential regulatory mechanisms in HCC. This study conducted comprehensive analyses using various bioinformatics tools and databases. Initially, differentially expressed genes related to HCC were identified from the GEO database, and the expression of AKR1B10 in HCC and other cancers was compared using TIMER and GEPIA databases, with validation of its specificity in HCC tissue samples using the HPA database. Furthermore, the relationship of AKR1B10 expression with clinicopathological features (age, gender, tumor size, staging, etc.) of HCC patients was analyzed using the TCGA database's LIHC dataset. The impact of AKR1B10 expression levels on patient prognosis was evaluated using Kaplan-Meier survival analysis and the Cox proportional hazards model. Additionally, the correlation of AKR1B10 expression with tumor biology-related signaling pathways and tumor immune microenvironment was studied using databases like GSEA, Targetscan, and others, identifying microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) that regulate AKR1B10 expression to explore potential regulatory mechanisms. Elevated AKR1B10 expression was significantly associated with gender, primary tumor size, and fibrosis stage in HCC tissues. High AKR1B10 expression indicated poor prognosis and served as an independent predictor for patient outcomes. Detailed mechanism analysis revealed a positive correlation between high AKR1B10 expression, immune cell infiltration, and pro-inflammatory cytokines, suggesting a potential DANCR-miR-216a-5p-AKR1B10 axis regulating the tumor microenvironment and impacting HCC development and prognosis. The heightened expression of AKR1B10 in HCC is not only related to significant clinical-pathological traits but may also influence HCC progression and prognosis by activating key signaling pathways and altering the tumor immune microenvironment. These findings provide new insights into the role of AKR1B10 in HCC pathogenesis and highlight its potential as a biomarker and therapeutic target.
Subject(s)
Aldo-Keto Reductase Family 1 member B10 , Carcinoma, Hepatocellular , Gene Expression Regulation, Neoplastic , Liver Neoplasms , Tumor Microenvironment , Humans , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/metabolism , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Liver Neoplasms/immunology , Liver Neoplasms/mortality , Liver Neoplasms/metabolism , Male , Female , Prognosis , Aldo-Keto Reductase Family 1 member B10/genetics , Aldo-Keto Reductase Family 1 member B10/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Middle Aged , Kaplan-Meier Estimate , Aldo-Keto Reductases/genetics , Aldo-Keto Reductases/metabolism , Gene Expression Profiling , Computational Biology/methodsABSTRACT
In this work, a sustainable 3D carbon aerogel (AO-WPC) is prepared from waste paper (WP), and used for efficient antibiotics removal from water. The AO-WPC aerogel shows good mechanical property and can recover after 100th of 30 % compression strain. The specific surface area of AO-WPC aerogel is up to 654.58 m2/g. More importantly, this aerogel reveals proper pore size distribution, including micro sized macropores between carbon fibers and intrinsic nano scale mesopores (11.86 nm), which is conducive to remove antibiotics from water. Taking tetracycline (Tc) as an example, the maximum adsorption capacity and adsorption rate of AO-WPC for Tc are as high as 384.6 mg/g and 0.510 g/(mgâ§min), respectively, which exhibits significant advantages over most of the recent absorbents, and the adsorption toward Tc reveals good resistance to various environmental factors, including pH, various ions, and dissolved organic matter (DOM). Moreover, good thermal stability enables the AO-WPC aerogel to be regenerated through simple burning, and the adsorption capacity of Tc only decreases by 10.4 % after 10 cycles. Mechanism research shows that hydrogen bonding and π-π electron-donor-acceptor (EDA) interaction play the important role in the adsorption. The excellent mechanical property and adsorption performance imply good practical prospect of the AO-WPC aerogel.
Subject(s)
Anti-Bacterial Agents , Carbon , Gels , Paper , Tetracycline , Water Pollutants, Chemical , Water Pollutants, Chemical/chemistry , Anti-Bacterial Agents/chemistry , Adsorption , Carbon/chemistry , Gels/chemistry , Tetracycline/chemistry , Tetracycline/isolation & purification , Water Purification/methods , Industrial WasteABSTRACT
The present study aimed to investigate the efficacy of hysteroscopic levonorgestrel-releasing intrauterine device (LNG-IUD) fixation surgery in the treatment of adenomyosis through a cohort study. The cohort study was performed at the Affiliated Jinhua Hospital of Wenzhou Medical University (Jinhua, China). A total of 31 women with adenomyosis were initially recruited from June 2020 to June 2022 and divided into an experimental group and a control group. The experimental group underwent hysteroscopic LNG-IUD fixation surgery and the control group underwent conventional implantation of the levonorgestrel-releasing intrauterine system. The assessed efficacy outcomes included the time of LNG-IUD expulsion, postoperative vaginal bleeding time, dysmenorrhea, and the menstrual blood loss score (MBLS). A total of 31 participants completed the research. The LNG-IUD expulsion rate was 6.25 and 60% (P<0.05) in the experimental and control group, respectively. The LNG-IUD in place time was 20.50 months (Q1, 15.75; Q3, 24.00) in the experimental group and 10.00 months (Q1, 6.50; Q3, 15.00) in the control group (P<0.05); the time of vaginal bleeding after surgery in the experimental and control groups were 12.50 days (9.25, 16.25) and 120.00 days (75.00, 120.00), respectively (P<0.05). Multiple-factor Cox regression analysis revealed that the LNG-IUD expulsion in patients with adenomyosis is associated with the hysteroscopic LNG-IUD fixation surgery [hazard ratio (HR), 1954.09], uterine cavity depth (HR, 16.63), MBLS (HR, 1.14), history of gonadotropin-releasing hormone agonist treatment in the previous 6 months (HR, 2.10), history of vaginal delivery (HR, 1.79) and history of cervical laceration (HR, 3.69). In conclusion, hysteroscopic LNG-IUD fixation reduces the rate of LNG-IUD expulsion, prolongs the time of LNG-IUD in the uterine cavity, reduces the time of postoperative vaginal bleeding, relieves the symptoms of dysmenorrhea and reduces the menstrual volume in the patients with adenomyosis. The present trial was retrospectively registered in the Chinese Clinical Trial Registry on 28th December 2023 (registration no. ChiCTR2300079233).
ABSTRACT
Circular RNA (circRNA) represents a type of newly discovered non-coding RNA, distinguished by its closed loop structure formed through covalent bonds. Recent studies have revealed that circRNAs have crucial influences on host anti-pathogen responses. Yellow catfish (Pelteobagrus fulvidraco), an important aquaculture fish with great economic value, is susceptible to Aeromonas veronii, a common aquatic pathogen that can cause acute death. Here, we reported the first systematic investigation of circRNAs in yellow catfish, especially those associated with A. veronii infection at different time points. A total of 1205 circRNAs were identified, which were generated from 875 parental genes. After infection, 47 circRNAs exhibited differential expression patterns (named DEcirs). The parental genes of these DEcirs were functionally engaged in immune-related processes. Accordingly, seven DEcirs (novel_circ_000226, 278, 401, 522, 736, 843, and 975) and six corresponding parental genes (ADAMTS13, HAMP1, ANG3, APOA1, FGB, and RALGPS1) associated with immunity were obtained, and their expression was confirmed by RT-qPCR. Moreover, we found that these DEcir-gene pairs likely acted through pathways, such as platelet activation, antimicrobial humoral response, and regulation of Ral protein signal transduction, to influence host immune defenses. Additionally, integrated analysis showed that, of the 7 immune-related DEcirs, three targeted 16 miRNAs, which intertwined into circRNA-miRNA networks. These findings revealed that circRNAs, by targeting genes or miRNAs are highly involved in anti-bacterial responses in yellow catfish. Our study comprehensively illustrates the roles of circRNAs in yellow catfish immune defenses. The identified DEcirs and the circRNA-miRNA network will contribute to the further investigations on the molecular mechanisms underlying yellow catfish immune responses.